Rod shaped body and medical device

ABSTRACT

The present invention relates to a medical device. In particular, the present invention concerns a medical device which can be detected by means of magnetic resonance imaging (MRI).

The present invention relates to a rod shaped body and a medical device.In particular, the present invention concerns a medical device which canbe detected by means of magnetic resonance imaging (MRI).

WO 2007/000148 A2 discloses a rod shaped body serving for the design ofmedical devices such as catheters or guidewires. This rod shaped bodyconsists of one or more filaments and a non-ferromagnetic matrixmaterial enclosing the filaments. A doping agent made of particles whichcreate MRI artifacts is embedded in the matrix material.

A detailed explanation of MRI can be found in the Internet athttp://en.wikipedia.org/wiki/Magnetic_Resonance_Imaging.

DE 101 07 750 A1 describes a guidewire which is supposed to be suitablefor MRI. This guidewire comprises a core made of a metallic distal part.Cords made from an electrically non-conductive polymer material arearranged between an outer jacket and the core. This polymer material issupposed to be reinforced with glass fibers or carbon fibers. Carbonfibers, however, are electrical conductors so that they cannot be usedin MRI.

Further medical devices are known from EP 1 206 945 A1. These areequipped with paramagnetic metallic compounds and/or a paramagneticmetal so that they are visible in MRI.

EP 0 659 056 B1 discloses a contrast agent adapted for MRI of a sample.This contrast agent comprises a suspension of particles possessingpositive magnetic susceptibility characteristics and particlespossessing negative magnetic susceptibility characteristics. Therelative amounts of these two kinds of particles are adjusted such thatthe positive magnetic susceptibility offsets the negative magneticsusceptibility to such an extent that the resulting suspension hassubstantially zero magnetic susceptibility. This eliminatessubstantially all imaging artifacts and delimitates the signal orartifact, respectively, almost sharply to the object itself.

WO 87/02893 discloses poly-chelating substances for imaging enhancementand spectral enhancement for MRI. These substances comprise differentcomplexes in which metal ions, in particular gadolinium ions, areimmobilized.

The relaxivity of gadolinium(III) complexes is explained in chapter1.6.1 of the Ph.D thesis (Inaugural Dissertation) by Daniel Storch,entitled “Neue, radioaktiv markierte Magnet-Resonanz-aktiveSomatostatinanaloga zur besseren Diagnose and zielgerichtetenRadionuklidtherapie von neuroendokrinen Tumoren”, Basel, 2005. Theparamagnetic relaxation of the water molecules located in the vicinityof the gadolinium(III) ion is the result of thedipole-dipole-interaction between the nuclear spin and the fluctuatinglocal magnetic field of the MRI scanner, caused by the unpairedelectrons of the gadolinium(III) ion. The magnetic field around theparamagnetic center, i.e. the gadolinium(III) ion, decreases withincreasing distance. Therefore, it is essential to locate the protons inclose proximity to the metal ion. For gadolinium(III) complexes thismeans that the water molecules are to be transported into the firstcoordination sphere of the metal ion. These “inner-sphere” H₂O moleculesare exchanged with the surrounding water molecules and in this waytransmit the paramagnetic effect.

DE 100 40 381 C1 discloses fluoroalkyl-containing complexes withresidual sugars. These complexes can be provided with paramagnetic metalions so that they can serve as contrast agents in magnetic resonanceimaging. These metal ions are in particular the bivalent and trivalentions of the elements of the atomic numbers 21 to 29, 42, 44 and 58 to70. Suitable ions are, for instance, the chromium(III), iron(II),cobalt(II), nickel(II), copper(II), praseodymium(III), neodymium(III),samarium(III) and ytterbium(III) ions. Gadolinium(III), erbium(III),dysprosium(III), holmium(III), erbium(III), iron(III) and manganese(II)ions are particularly preferred because of their strong magnetic moment.

EP 1 818 054 A1 discloses the use of gadolinium chelates for the purposeof marking cells.

U.S. Pat. No. 6,458,088 B1 describes a guidewire provided for MRI, thisguidewire comprising a glass body. The glass body is provided with aprotective layer which is made of polymeric material and additionallycan be reinforced with fibers. The distal end of the guidewire can bemade from a metal section such as nitinol. This metal section shouldhave a length which is clearly shorter than the wavelength of themagnetic resonance field.

WO 2005/120598 A1 discloses a catheter guidewire comprising a PEEK core.This core is covered by a coating. The coating contains a contrastagent. The contrast agent is iron powder having a grain size of lessthan 10 μm.

WO 97/17622 discloses a medical device comprising an electricallynon-conductive body which is covered by an ultra-thin coating made of anelectrically conductive material so that the medical device is visiblein MRI without unduly affecting the image.

WO 99/060920 A2 and WO 2002/022186 A1 each describe a coating for amedical device comprising a paramagnetic ion which is complexed in thecoating. The paramagnetic ion in particular is gadolinium. This coatingis visible in MRI.

WO 2009/141165 A2 discloses a medical device which can be inserted intoa human or animal body. The medical device has a body which comprises atleast one rod shaped body having poor electrical conductivity and beingformed from a matrix material and non-metallic filaments. These rodshaped bodies correspond insofar to the one described in WO 2007/000148A2.

The rod shaped body is doped with X-ray marker particles and the medicaldevice further comprises an MR marker. The MR marker can be provided bymeans of a further rod shaped body or by means of an immobilized activeMR marker on the surface area of the medical device.

Such rod shaped bodies are very advantageous for use in medical deviceswhich can be readily produced by embedding one or more such rod shapedbodies in an envelope polymer wherein the rod shaped bodies may containdifferent doping materials. By using different types of rod shapedbodies medical devices having different doping materials (=markers) canbe designed and produced. Hence, these have different properties withrespect to their visibility in X-ray or MRI examinations. Thesedifferent medical devices can be produced by the very same productionmethod and consecutively in the same production run by simply exchangingone or several of the rods. Therefore, even if these medical devices areproduced in small quantities it is possible to economically manufacturedifferent types of medical devices.

In Shu Chen et al.; “Engineered Biocompatible Nanoparticles for in VivoImaging Applications”; American Chemical Society 2010, 132, 15022-15029,the use of FePt nanoparticles as contrast agent for MRI is described.

One object of the present invention is to further improve such rodshaped bodies for being embedded in a matrix material of a medicaldevice.

A further object of the present invention is to provide such rod shapedbody or a medical device comprising at least one such rod shaped bodywhich can be employed safer than the known medical devices.

A further object of the present invention is to provide such rod shapedbody or a medical device having optimized markers.

A further object of the present invention is to provide a medical devicewhich can be inserted into a human or animal body and is very versatilein its use in MRI examinations.

A further object of the present invention is a medical device having acoating stably attached to the outer surface.

The subject matter of the independent claims solve one or more of theseobjects. Advantageous embodiments are indicated in the sub-claims.

Throughout the specification the term “medical device” is used in abroad sense to refer to any medicinal device, tool, instrument or otherobject. The medical devices of the present invention are particularlyuseful as any type of guidewires, catheters (including vascular andnon-vascular, esophageal, peritoneal, peridural, nephrostomy catheters),tubes, mandrins, stylets, stents, implants, grafts, biopsy needles,puncture needles, cannulae, intralumenal medical devices, endotrachealtubes, and ablation devices. They can be introduced or implanted in a“target” or “target object”. The target or target object is all or apart of the human or animal body. The medical device of the presentinvention particularly may be brought into cavities of the target(object). These cavities are particularly blood vessels, neuronal ways,any organs (whole or part) or tissues (whole or part). The medicaldevice of the present invention may also be used as an accessory partproviding MRI functionality and/or applicability to other medicaldevices.

According to a first aspect a rod shaped body comprises

-   -   one or more non-metallic filaments and    -   a non-ferromagnetic matrix material,        wherein the matrix material encloses and/or agglutinates the        filaments, and marker particles for generating a signal in an        X-ray or magnetic resonance imaging process,        wherein at least one of said non-metallic filaments is a        ht-fiber.

A ht-fiber is a high tenacity fiber. Typical examples of ht-fibers arearamide fibers and UHMWPE fibers (ultra high molecular weightpolyethylene fibers). Ht-fibers have a tensile strength of at least 20cN/tex. Optionally the ht-fibers have a tensile strength (tenacity) ofat least 23 cN/tex and in particular of at least 30 cN/tex.

A ht-fiber is highly flexible and provides a high tensile strength.Thereby, it is ensured that even if the rod breaks in the human oranimal body during the medical intervention the broken parts are stillconnected by the ht-fiber and can be safely pulled out.

Furthermore, the ht-fiber provides a certain rigidity to the rod.However, glass fibers are stiffer than ht-fibers so that a rod havingboth ht-fibers and glass fibers is preferred. Such a rod can beoptimally adjusted with respect to rigidity versus flexibility and withrespect to torsional stiffness.

According to a second aspect of the present invention, a rod shaped bodycomprises

-   -   one or more non-metallic filaments and    -   a non-ferromagnetic matrix material,        wherein the matrix material encloses and/or agglutinates the        filaments, and marker particles for generating a signal in an        X-ray or MRI process. This rod shaped body is characterized in        that the one or more non-metallic filaments extend along the        major part of the rod shaped body.

Such long filaments provide a high strength in longitudinal direction tothe rod shaped bodies.

The non-metallic filaments are electrically non-conductive filaments sothat they can be used during MRI measurements. Concluding, the term“non-metallic filaments” as used in the present text excludes anyelectrically conductive filaments such as a thin metal wire or a carbonfilament.

Advantageously the filaments form a roving which comprises severalfilaments being arranged in parallel to each other.

However, it is also possible that the filaments of a rod shaped bodyform a yarn which means that the filaments are drilled and/or braided.

According to a further aspect of the present invention a medical devicecomprises one or more rod shaped bodies, each comprising

-   -   one or more non-metallic filaments and    -   a non-ferromagnetic matrix material,    -   wherein the matrix material encloses and/or agglutinates the        filaments and marker particles for generating a signal in an        X-ray or magnetic resonance imaging process, and an envelope        polymer in which the one or more rod shaped bodies are embedded,        wherein a cord is embedded either in the matrix material or in        the envelope polymer, wherein the cord is more flexible than the        non-metallic filaments.

The stiffness of the medical devices and hence of the rod shaped bodiesin lateral direction has to be in a certain range which allows to easilyguide the medical device through a given cavity of the human or animalbody, e.g. a blood vessel. Therefore, the lateral stiffness is limitedand it can occur under extreme conditions that the non-metallicfilament(s) in the rod(s) may break. In such a case the broken parts ofthe rod(s) are still connected by the cord whereby additionally theenvelope polymer remains intact. The medical device still can be safelyremoved as one part from the body cavity without the risk of lost partsin the blood stream or in body tissue. Thus the cord represents a meansfor increased safety of the medical devices.

The cord preferably is a thin cord having a high tensile strength.Suitable cords are e.g. polyamide filaments, ht-fibers, polyethyleneterephthalate (PET) filaments, rayon filaments (e.g. HL fiber), cottonfilaments, or hemp filaments having a diameter preferably of 0.05 mm to0.2 mm. If the cord comprises one or more ht-fibers then these ht-fiberscan simultaneously act as the non-metallic filaments of the rod shapedbody. Of course it is possible to provide the cord in the medical deviceindependent of the rod shaped bodies of said device.

According to another aspect of the present invention a medical devicecomprises several rod shaped bodies, each comprising

-   -   one or more non-metallic filaments and    -   a non-ferromagnetic matrix material,    -   wherein the matrix material encloses and/or agglutinates the        filaments and marker particles for generating a signal in an        X-ray or magnetic resonance imaging process, and an envelope        polymer in which the rod shaped bodies are embedded,        wherein the rod shaped bodies are arranged in different        positions with respect to the center of the medical device and        the rod shaped bodies which are positioned closer to the center        of the medical device comprise non-metallic filaments having a        higher tensile modulus than the non-metallic filaments of the        rod shaped bodies which are positioned more distant to the        center of the medical device.

Such a medical device having non-metallic filaments with a higherstrength in the rods in its center section than the strength of thenon-metallic filaments of the rods in the more peripheral sectioncombines both a high flexibility as well as a high strength.

According to a further aspect the medical device comprises an elongatedbody, such as a guidewire, catheter or tube, made of a polymer materialand the polymer material encloses a passive-negative MRI markerconsisting of marker particles for generating an artifact in a magneticresonance imaging process, wherein the passive-negative MRI marker islocated only in a central section of the medical device.

As the marker is located in a central section it is covered by acircumferential section which does not contain any MRI marker.Therefore, there is a certain distance between the MRI marker and theouter surface of the medical device. In use the MRI marker is kept inthis distance to water molecules surrounding the medical device. Thelarger this distance is the smaller are the artifacts in the MRI imagingprocess.

The distance of the passive-negative MRI marker to the outer surface ofthe medical device is preferably at least 0.1 mm, more preferably atleast 0.2 mm, or at least 0.3 mm.

Such a medical device can comprise non-metallic filaments and saidpolymer material forms a non-ferromagnetic matrix material enclosingand/or agglutinating the filaments.

Such a medical device can also comprise the above described rod shapedbodies containing said MRI marker.

Such a medical device can be a a guidewire having a rod shaped bodycomprising a passive-negative MRI marker and being positioned at thecenter of the guidewire.

Such a device can also be a catheter or a tube having either at leastone rod shaped body comprising a passive-negative MRI marker and beingpositioned at the inner section of the catheter or the tube, or isembodied of at least two concentric layers, wherein only the innermostlayer comprises a passive-negative MRI marker.

If the medical device is embodied as said catheter or tube having atleast two concentric layers, one of said layers can be reinforced bynon-metallic filaments being twisted, braided, or woven to a spatialstructure. Such a spatial structure is particularly preferable incombination with ht-fibers. Ht-fibers are flexible and have a hightensile strength. As in such a spatial structure the filaments arerunning in different directions in the body of the medical device thehigh tensile strength causes also a high stiffness of the compositematerial consisting of the fibers and the matrix material.

According to a further aspect of the present invention a medical devicecomprises

-   -   several rod shaped bodies for reinforcing the medical device,        and    -   an envelope polymer in which the rod shaped bodies are embedded,        wherein the medical device comprises marker particles for        generating an artifact in an MRI process, and the envelope        polymer is a soft polymer or rubber material or PVC.

The rod shaped bodies according to this aspect of the invention can beembodied according to the other aspects of the present invention and/orthe non-metallic reinforcing filaments may be glass fibers.

The markers can be incorporated into the rods and/or into the envelopepolymer.

The specific envelope polymer according to this further aspect of thepresent invention has a relaxation time significantly shorter than thatof water but distinctly longer than that of a hard polymer such as epoxyresin. Therefore, different from hard polymers, with appropriateparameter settings and a short echo time (preferably <100 ms, morepreferably <50 ms, even more preferably <10 ms, and most preferably <1ms) this envelope polymer can be visualized in an MRI process.Particularly, the protons of this envelope polymer can be detected withan MRI echo time that is different from the one used for detecting theprotons of water. Therefore, by using two different echo times it ispossible to record two different images of the same object with the sameview wherein one image clearly visualizes the medical device (bymeasuring relaxation of the protons in the envelope polymer) and theother image the body tissue (by measuring relaxation of the protons inwater and lipds contained in the body tissue or blood). Both images canbe superimposed so that the physician obtains combined information inone image. Due to the detection of protons in the soft polymer and notin water molecules surrounding the medical device a more confined andsignificantly sharper artifact can be achieved which is almost limitedto the actual diameter of the medical device.

This envelope polymer preferably has a T1 relaxation time of 1 to 100ms, more preferably 1 to 500 ms, and most preferably 1 to 1000 ms, and aT2 relaxation time preferably of 0.1 to 1 ms, more preferably 0.1 to 5ms and most preferably 0.1 to 10 ms.

In a further embodiment of the present invention the medical device hasa stably attached coating on its outer surface. This coating preferablyis lubricious. The stably attached coating material is obtained bycompounding the envelope polymer with one or more chemical compoundshaving functional groups, preferably carboxy groups or amino groups.Embedding the rods in this modified envelope polymer preferably isachieved by an extrusion process. Subsequently the surface functionalgroups, preferably the carboxy groups/amino groups, are reacted withother functional groups, preferably with amino groups/carboxy groups,respectively, to obtain a covalent bond, preferably an amide bond. Theresidual functional groups (e.g. the remaining carboxy/amine groups) arethen chemically crosslinked by a crosslinker.

The above described different aspects of the invention can be combinedwith each other.

The invention will now be exemplified in more detail on the basis of theembodiments illustrated in the drawings in which:

FIG. 1 a shows a rod shaped body according to the invention in aperspective view,

FIG. 1 b shows the rod shaped body according to FIG. 1 a in across-sectional view,

FIGS. 2 a, 2 b show guidewires according to the present invention incross-sectional views,

FIGS. 3 a, 3 b show catheters according to the present invention incross-sectional views,

FIGS. 4 a to 4 h show images which have been created by the testequipment by means of MR or X-ray imaging,

FIG. 5 list of medical devices,

FIGS. 6 and 7 show images which have been created using the test samplesor combinations of the test samples by means of MR imaging.

Some of the present prototypes are realized with aramide fibers. In thefollowing detailed description of the present invention the terms“aramide fiber” and “aramide filaments” are used as synonym toht-fibers. Aramide fibers were chosen due to its tensile strength. Thusit is clear for someone skilled in the art that the aramide fibers canbe replaced by other non electrically conductive fibers having the sameor even better tensile strength.

The first aspect of the present invention relates to a rod shaped body 1(in the following: rod) which forms an intermediate product forproducing medical devices. The rod shaped body according to the presentinvention is a further development of the rod shaped bodies as describedin WO 2007/000148 A2 and WO 2009/141165 A2. Therefore, full reference ismade to the disclosure of these documents and those documents areincorporated here by reference.

The rod 1 comprises one or more non-metallic filaments 2 and anon-ferromagnetic matrix material 3 (in the following: matrix). Thenon-metallic filaments 2 are electrically non-conductive filaments.Electrically conductive filaments would lead to electric current in andheating of the guidewire induced by the magnetic and RF fields during MRimaging. Such rods can comprise metal particles but these particles mustbe separated from each other so that they do not create electricallyconductive sections of more than 10 to 15 cm, preferably not more than 5to 10 cm. The matrix material encloses and/or agglutinates thefilaments. The rods 1 are usually doped with marker particles forgenerating a signal in an X-ray or MR imaging process. These particlesare embedded in the matrix 3. However, it can also be desirable to havean undoped rod 1 without any marker particles.

A basic characteristic and advantage of the rods 1 is that differentrods 1 can be doped with different marker particles, whereas in amedical device differently doped and/or undoped rods 1 can beincorporated. This will be explained in more detail below in thedescription of the different versions of medical devices according tothe present invention. Simply by use of differently doped rods variousmedical devices having different characteristics in X-ray or MR imagingprocesses can be easily and cost-efficiently manufactured in the sameprocess by replacing one rod by another one.

FIG. 1 a schematically displays a rod 1 in a perspective view. Thefilaments 2 of the rod 1 are long filaments 2 which are directed in thelongitudinal direction of the rod 1. These filaments 2 extend along themajor part of the rod 1. This means that the length of the filaments 2is at least half of the length of the rod 1. Preferably, the length ofthe filaments 2 extends along the total length of the rods 1 or at least80% of the total length of the rods 1.

Such long filaments 2 provide a high strength to the rods 1 inlongitudinal direction. Medical devices comprising these rods frequentlyare designed for being introduced into a blood vessel, an organ (e.g.heart, liver, kidney or lung) or the brain. Therefore, a strong forcecan be applied to these medical devices in longitudinal direction duringintroduction of these devices into the body cavity or when pulling themout thereof. This force is taken up by the rods 1.

On the other hand the medical devices have to provide a certainflexibility to advance them along curves of the body cavity. Byarranging the filaments 2 in longitudinal direction of the rods 1, rodsare obtained having both a high stability/strength in longitudinaldirection and an appropriate flexibility in lateral direction.

The filaments 2 are usually made of glass fibers. It is also possiblethat the reinforcing fibers are ceramic fibers, polyamide or aramid,e.g. Kevlar® fibers, as long as the fibers provide the necessarystrength in longitudinal and lateral direction. It is possible to alsouse other kinds of fibers as long as the fibers do not provide electricconductivity. Long fibers of electrically conductive material cannot beincorporated into medical devices being used in an MRI process.

Glass fibers are available in different qualities. These differentqualities are called E-glass (E=electric), S-glass (S=strength), R-glass(R=resistance), M-glass (M=modulus), D-glass

(D=dielectric), C-glass (C=corrosion), ECR-glass (E-glass corrosionresistant). The tensile strength, the tensile modulus and the elongationto failure of E-glass, D-glass and R- or S-glass is shown in thefollowing table:

Tensile strength Tensile modulus Elongation to failure (MPa) (GPa) (%)E-glass 3400 73 7.7 D-glass 2500 55 4.5 R- or S-glass 4400 86 5.1

Saint-Gobain offers under the trade name Quartzel® a glass fiber witheven a higher strength, namely a tensile strength of 6000 MPa, a tensilemodulus of 78 GPa and an elongation to failure of 7.7%.

A group of several filaments 2 being arranged in parallel to each otheris called a roving. The rod 1 is produced by means of themicro-pultrusion process. Thereby such a roving is pultruded togetherwith the matrix material in which the marker particles can be contained.The amount of filaments has a strong influence on the mechanicalproperties of the rods.

Yarns can be used instead of rovings for the production of the rods 1.In such yarns the filaments 2 are drilled or braided. However, rovingsare preferred as the drilled or braided structure of the yarns may causea corresponding structure at the surface of the rods. Rods having asmooth surface instead of such a structured surface are preferredbecause it is easier to use them in a subsequent extrusion process toobtain a smooth surface of the respective medical device.

Glass fibers usually are quantified and characterized in “Tex” whichmeans g/m. Filaments 2 used in the rods 1 usually are in the range of 10to 100 Tex, more preferred 30 to 70 Tex. The diameter of the rodsusually is in the range of 0.10 mm to 0.30 mm.

The amount of the matrix material, which preferably is epoxy resin,defines the capacity for incorporated marker particles. Therefore, it ispreferred to have several filaments uniformly distributed or preferablylocated at the circumferential section of the rod to provide the rodwith a high mechanical strength without occupying a to large part of thecross section area of the rod. The lower the number of filaments theweaker is the mechanical strength of the rod. This even applies if thelower number of filaments is compensated by a higher diameter of thefilaments. Therefore, it is preferred that the number of filaments is atleast four, or more, e.g. at least six or at least ten.

According to a further aspect of the present invention the rod 1comprises in addition to the filaments 2 a cord 4. The cord 4 isembedded in the matrix material 3. The cord 4 consists of a materialwith a higher flexibility than the filaments 2 such as polyamidefilaments, aramide filaments, polyethylene terephthalate (PET)filaments, rayon filaments (e.g. HL fiber), cotton filaments, or hempfilaments. The cord 4 extends along the total rod and is directed in thelongitudinal direction of the rod. Such a cord does not break if it isbent. On the other hand the longitudinal strength of such a cord 4having the same cross sectional area as a filament 2 usually is weakerthan the longitudinal strength of the filaments 2.

If the rod 1 or a medical device incorporating such a rod 1 breaks, thebroken parts are still connected by means of the cord 4. Thereby, it isensured that even if such a breakage occurs in the human or animal bodyduring the medical intervention the broken parts can be safely pulledout. The cord 4 is advantageously arranged in the center of the rod 1.

Aramide filaments provide the functions of both the cord as well as thenon-metallic filaments. Thus, a medical device comprising one rod havingan aramide filament which is arranged in parallel, twisted, braided,woven or in another type of assembly, is preferred. Twisted, braided,woven filaments form a spatial structure which is preferred incombination with a flexible filament such as aramide filaments.

Aramide filaments are flexible and have a high tensile strength. As insuch a spatial structure the filaments are running in differentdirections in the body of the medical device the high tensional rigidityof the filaments causes also a high stiffness of the composite materialconsisting of the fibers or filaments, respectively, and the matrixmaterial.

In the following the mechanical structure of medical devices comprisingseveral of the rods 1 is explained:

FIGS. 2 a and 2 b each show a guidewire 5 in a cross-sectional view.Such a guidewire 5 is a medical device which frequently is inserted intoa blood vessel whereby preferably a flexible tip at the distal end ofthe guidewire supports easy access to a certain place in a human oranimal body. If the position of the guidewire is correct then othermedical devices can be advanced along the guidewire.

The medical device, particularly the guidewire, according to the presentinvention comprises several rods 1 and an envelope polymer 6. Theenvelope polymer 6 preferably is a biocompatible material. Suchbiocompatible materials are available on the market e.g. under the tradenames Mediprene® or Tecoflex™. Tecoflex™ is an elastic polymer materialwhich is based on polyurethane (PU). Mediprene® is a thermoplasticelastomer made from SEBS (styrene-ethylene-butylene-styrene-elastomer)which is primarily used for medical purposes. Mediprene is offered byElasto AB, Sweden. Other appropriate polymers are e.g. polyethylene,polypropylene, EVA, PVP and silicone. The envelope polymer can also bemade from other biocompatible materials, such as a soft biocompatiblepolymer material or rubber material or soft PVC.

The flexible and elastic envelope polymer 6 provides a certain shape tothe medical device and encloses the rods. Hence, the medical devicesconsist of a multi-composite material comprising the rods 1 as a kind ofreinforcing material and the envelope polymer 6 as embedding andagglutinating material. The mechanical properties of a medical deviceare mainly defined by the mechanical properties, the number, thedimensions, and the arrangement of the rods 1.

In a preferred embodiment the envelope polymer is modified bycompounding, i.e. mechanically mixing, it with chemical compounds havingone or more functional groups, preferably amino and/or carboxy groups.These chemical compounds are preferably polycarboxylic acids (e.g.polyacrylic acids), polyvinylamine, polyethyleneimine, acrolein-acrylicacid copolymer or polyallylamine. Particularly preferred is a compoundof Mediprene® and polycarboxylic acid. Most preferably a sodium saltsolution of polycarboxylic acid (e.g. POC AS 5060, Evonik Industries,Essen, Germany) is blended with Mediprene® polymer to obtain an amountof 5, 10, 20, 30 or 40 or more than 40% (w/w) POC in Mediprene®. Allamounts therebetween are also suitable and may be used. This modifiedenvelope polymer is then used in an extrusion process to embed andagglutinate the rods. After the extrusion the free carboxy groups at thesurface are reacted preferably with polyvinylamine or other polyaminopolymers to result in an amide linkage. Remaining free amino groups arethen crosslinked preferably with a short-chain (e.g. C₁-C₆) hydrophilicalpha-omega homobifunctional crosslinker to provide the stably attached,preferably lubricious, coating at the surface of the medical device.These modified surfaces are suitable to incorporate passive-positivemarkers as defined and described below (e.g. gadolinium (Gd) ions orcomplexes, or cerium (Ce), praseodymium (Pr), neodymium (Nd), promethium(Pm), samarium (Sm), europium (Eu), terbium (Tb), dysprosium (Dy),holmium (Ho), erbium (Er), thulium (Tm), ytterbium (Yb) and lutetium(Lu) ions or complexes).

According to the embodiment shown in FIG. 2 a there are a central rod1/1 and peripheral rods 1/2. The central rod is positioned in the centerof the guidewire 5. The peripheral rods 1/2 are positionedcircumferentially to the central rod 1/1 and the lateral surface of theguidewire 5. The embodiment comprises six peripheral rods 1/2 which areequally spaced apart from each other. The filament content of thecentral rod 1/1 is 66 Tex. The diameter of the central rod is about 0.20mm to 0.30 mm. The filament content of the peripheral rods 1/2 is 33 Texand the diameter is about 0.17 to 0.20 mm. The diameter of the guidewire5 is about 0.81 mm (0.032 inch). In a stiffer version of this guidewirethe diameter of the guidewire is increased to about 0.88 mm (0.035inch). The filament content can be increased up to at least 100 Tex forthe central rod 1/1 and up to at least 45 Tex for the peripheral rods1/2.

The embodiment shown in FIG. 2 a comprises furthermore two cords 4 whichare embedded in the envelope polymer 6. These cords 4 have the samepurpose and function as the cords 4 which are embedded in the rods 1 asdescribed above. Having the cords 4 embedded in the envelope polymer 6,it is not necessary to use rods 1 having such a cord 4.

Providing the cords 4 in the envelope polymer 6 allows to use cords 4having a larger diameter as cords which are included in the rods 1.However, it is more difficult to produce the medical devices havingcords in addition to the rods. Such medical devices are produced byco-extrusion, wherein the envelope polymer 6 is extruded together withthe rods 1 and the cords 4.

FIG. 2 b shows another embodiment of a guidewire 5 comprising onecentral rod 1/1 and three peripheral rods 1/2. In this guidewire 5 threecords 4 are embedded in the envelope polymer 6. The central rod 1/1 hasa filament content of 33 Tex and has a diameter of about 0.20 mm. Theperipheral rods 1/2 also have a filament content of 33 Tex but have asmaller diameter of about 0.17 mm. The total diameter of the guidewire 5is 0.81 mm. The guidewire according to the embodiment of FIG. 2 b has alower stiffness in comparison to the guidewire of FIG. 2 a. The filamentcontent can be decreased down to at least 12 Tex or lower for thecentral rod 1/1 and the peripheral rods 1/2.

The embodiments shown in FIGS. 2 a and 2 b are mere examples. Anadvantage of the present invention is that due to the compositestructure of the medical devices the mechanical properties, e.g.guidewires, can be individually adapted to the required interventionalapplication by variation of the geometries (i.e. number, dimensioningand positioning of the rods 1/1 and 1/2). Furthermore, guidewires maynot contain a central rod 1/1 but only peripheral rods 1/2. Minimally, aguidewire contains only one rod.

Actually there are the following classes of guidewires which areclassified only according to their mechanical properties:

1) Stiff or Super-Stiff Guidewires

A stiff or super-stiff guidewire has a diameter of 0.88 to 0.97 mm(0.035-0.038 inch). The central rod 1/1 has a fiber content of 66 Tex orhigher, wherein up to about 100 Tex can be appropriate. At least five,preferably at least 6 or more peripheral rods 1/2 are provided. Thefiber content of the rods is in the range of 20 to 40 Tex. The envelopepolymer 6 is preferably made of a polymer with a shore hardness of atleast 40D, preferably 60D and more preferably 72D.

2) Standard Guidewire

The standard guidewire typically has a diameter in the range of 0.81 to0.88 mm (0.032-0.035 inch). The central rod preferably has a fibercontent of 20 to 40 Tex. The standard guidewire preferably comprises 2to 4 peripheral rods 1/2. The peripheral rods preferably have a fibercontent of 20 to 40 Tex. The envelope polymer may be made of a soft,medium or hard polymer material. The softer the envelope polymer is, thestiffer the rods 1/1, 1/2 have to be designed. Due to the peripheralposition of the peripheral rods 1/2 a small increase of the stiffness ofthe peripheral rods significantly increases the total stiffness of theguidewire.

Therefore, the total stiffness of the guidewire can easily be adapted ina wide range by selecting different peripheral rods.

3) Standard Micro Guidewire

A standard micro guidewire has a diameter of about 0.36 to 0.41 mm(0.014-0.016 inch). The central rod has a fiber content of preferably 15to 33 Tex, more preferably 20 to 25 Tex. The micro guidewire preferablycomprises 1 to 3 peripheral rods. The fiber content of the peripheralrods preferably is about 10-20 Tex. The envelope polymer is preferablymade of a polymer material having a shore hardness below 72D, morepreferably below 60D and even more preferably below 40D. According toanother embodiment the standard micro guidewire comprises only one rodhaving a fiber content of preferably 50 to 100 Tex, more preferably 55to 80 Tex. This rod comprises a passive-positive MRI marker such as iron(Fe) particles. The concentration of the passive-positive MRI marker inthe matrix is in the range of 1:10 to 1:100 and preferably in the rangeof 1:40 to 1:60. The particle size of the passive-positive MRI markerparticle preferably is about 40 μm to about 65 μm.

4) Super Flexible Micro Guidewire

The super flexible micro guidewire has a diameter of about 0.25 to 0.36mm (0.010-0.014 inch) and preferably 0.28 to 0.33 mm (0.011-0.013 inch).It does not have a central rod. It comprises 2 or 3 peripheral rods. Theperipheral rods have a glass fiber content of preferably 10-20 Tex. Theenvelope polymer is preferably made of a polymer having a shore hardnessbelow 60D and more preferably below 40D.

5) Stiff Micro Guidewire

A stiff micro guidewire has a diameter of a about 0.25 to 0.46 mm(0.010-0.018 inch). It consists of one rod 1 without any envelopepolymer. The fiber content of the rod preferably is about 30 to 120 Tex,and in particular 60 to 100 Tex. To avoid disruptionof a brokenguidewire it is preferred that it comprises at least one aramidefilament. The stiff micro guidewire comprises preferably at least onearamide filament and at least one glass fiber and in particular, severalaramide filaments and several glass fibers. Such a combination ofdifferent filaments in one rod ensures that the rod does not disruptafter breakage and has a sufficiently high stiffness resulting from theglass fibers.

These classes of guidewires are typical examples. As mentioned abovereinforcing fibers for the rods, particularly glass fibers, areavailable in different qualities. If glass fibers with a higherstiffness or strength, respectively, are used then the stiffness can beaccordingly adapted by the mechanical properties resulting from theother materials of the guidewire, or from the number of the rods, orfrom the arrangement of the rods, or from the embodiment of the rods(particularly with respect to the fiber content and the diameter of therods). The above examples demonstrate that due to the multi-compositestructure the medical devices can be designed with a wide range ofmechanical properties. These are independent of the visibility in anX-ray and/or MR imaging process as described further below.

If a guidewire having a central rod and peripheral rods is bent then theperipheral rods are more elongated and compressed than the central rod.To improve the flexibility of the guidewire it is appropriate to havemore extensible glass fibers in the peripheral rods than in the centralrod, i.e. the glass fibers of the peripheral rods have a lower tensilemodulus than the glass fibers of the central rod. This means that thecentral rod provides a high stiffness and the peripheral rods provide ahigh elasticity so that the guidewire has the necessary flexibility andstiffness.

A medical device, particularly a guidewire, according to the presentinvention may comprise a flexible tip. Such a flexible tip can beproduced separately and be attached to the medical device by polymerwelding. The separately produced flexible tip is made of an elastic andweldable polymer e.g. polyurethane. The elastic tip is connected to therod by chemical welding or thermo welding. The stiffness of the flexibletip can increase from the end which is connected to the medical device,e.g. the guidewire, to the other (distal) end of the flexible tip.Preferably, the stiffness at the connected end is similar to thestiffness of the medical device, e.g. the guidewire. This can beachieved e.g. by reducing the diameter of the flexible tip in thedirection from the connected to the distal end.

In another embodiment the flexible tip of a medical device, esp. aguidewire, preferably is made by the following steps:

-   -   Grinding of a circumferential layer of the guidewire at one end        so that at least an outer part of the envelope polymer is        removed in this grinded section of the guidewire. Peripheral        rods or a part of a central rod can also be removed by grinding.        If the guidewire does not have an envelope polymer at least a        part of the rod is removed by grinding.    -   The grinded part of the guidewire is coated with a flexible        polymer material to form the flexible tip. The flexible polymer        material may distally extend beyond the grinded section so that        the flexible tip comprises a very soft end and an intermediate        section which is reinforced by rod material. The flexible        polymer can be any kind of flexible polymer, e.g. PEBAX 3533        SA01 med.

The length of the distal flexible tip preferably is 5 to 30 cm, morepreferably 8 to 20 cm and particularly preferably 10 to 15 cm.

Independent of whether the flexible tip is produced separately andattached to the rod, or whether it is produced by coating a core part ofthe rod, it is preferable that the flexible tip has the shape of a conewith a decreasing diameter from the connected to the distal end. Theflexible tip can be provided with an X-ray and/or MR marker. The markercan be one of the passive markers described below which is eitherblended to the material of the tip or which is coated to the tip.

The concentration of the MRI markers can be designed in such a way thatthe flexible tip causes MRI artifacts with a higher, the same or a lowerintensity than the residual part of the medical device.

Generally in the medical devices according to the present invention noelectrically conducting parts are used because they cause largeartifacts during MRI and lead to heating of the medical device. However,it can be appropriate to provide metallic particles or a metallic corein the flexible tip because then due to the artifacts the tip is clearlydistinguishable from the residual part of the medical device. Of courseit has to be accepted that the artifacts of the tip disturb the image inthe vicinity of the tip. Therefore, it can also be appropriate to havein the flexible tip a combination of the markers according to the belowdescribed embodiments. The tip can also be reinforced by means of shortglass fibers.

The gradient and the stiffness of the flexible tip can also be realizedby reducing the diameter of a central core of the flexible tip whereinthe core is made of a material which is harder than the main material ofthe flexible tip.

FIGS. 3 a and 3 b each show a cross-sectional view of a catheter 7. Sucha catheter 7 has the form of a tube wherein the catheter wall is made ofthe composite material comprising the rods 1 and the envelope polymer 6.As the rods 1 are placed further apart from the center of the catheterwhen compared to the arrangement in the guidewire 5 a smaller number ofrods 1 or less stiff rods 1 are sufficient to obtain the same strengthin lateral direction as in a corresponding guidewire 5.

The embodiment according to FIG. 3 a comprises three rods 1 each havinga filament content of 33 Tex and a diameter of about 0.17 mm to 0.20 mm.The embodiment of FIG. 3 b comprises six rods 1. In both embodiments atleast one cord 4 is embedded in the envelope polymer 6.

The design of the catheters according to the present invention can beclassified into the following two groups:

1) Standard Catheters (5F to 6F)

The diameter of catheters usually is defined by the unit “French”wherein 3 French correspond to 1 mm. A catheter having a diameter of 5Fto 6F (1.66 to 2.00 mm) according to the present invention is embodiedwith a wall thickness in the range of 0.20 to 0.30 mm. It comprises rodswith a fiber content of about 20 to 40 Tex and preferably 25 to 35 Tex.The number of rods is in the range of 3 to 8 and preferably 3, 5 or 6.

2) Micro catheters (2F to 4F)

A micro catheter has a diameter of 2F to 4F (0.66 to 1.33 mm) and thewall thickness is in the range of 0.10 to 0.25 mm. The rods have a fibercontent of about 10 to 20 Tex.

In a catheter the rods are spaced wider apart from each other than in aguidewire. Therefore, bending a catheter causes the rods to be bentstronger than in a guidewire. The rods of a catheter therefore shouldhave good elastic properties. The fibers for the rods of a catheter arepreferably made of a material, particularly a glass fiber, having a hightensile modulus (E-modulus) of at least 65 GPa and preferably of atleast 70 GPa.

An alternative embodiment of the catheter contains the rods braided intothe envelopepolymer.

Another alternative embodiment of a tube or catheter comprises at leasttwo concentric layers wherein the different layers may have the same ordifferent thickness and at least two layers consist of differentpolymers or polymer grades. These polymers may be chosen from anypolymer materials, e.g. Mediprene®, polyurethane (e.g. Tecoflex™),polyethylene, polypropylene, EVA, PVP, silicone, PEBAX, or PEEK. Suchtube or catheter comprises at least one MRI marker. One of the layerscan be provided with a passive-negative MRI marker. Preferably, only themost inner layer comprises a passive-negative MRI marker. Alternatively,the inner and/or the outer layer may be coated with a passive-positiveMRI marker.

This embodiment can be provided optionally with non-metallic filaments.The filaments can be twisted, braided, woven to a spatial structure,particularly to a tube like structure which is embedded in the polymermaterial. With such a spatial structure it is preferred that thefilaments comprise ht-fibers. A combination of ht-fibers and glassfibers allows to adjust the rigidity of the catheter or tube in a widerange.

FIG. 5 shows a table in which several medical devices are listed. Thistable contains four columns. In the first column the type of medicaldevice is defined. In the second column the design of the device isdescribed. The design of the device is defined by the number and thecharacteristics of the rods and by description of the envelope polymer.In the third column the filament content of the rods and thecorresponding diameters are specified. The fourth column providesexamples for appropriate interventional applications for thecorresponding medical device.

The medical devices listed in the table of FIG. 5 provide certainmechanical properties defined by the design of the device and the designof the rods as given in this table. The visibility of the medicaldevices can be adjusted individually and independent of the mechanicalproperties by doping the rods and/or the envelope polymer with suitablemarker particles as disclosed below.

This table discloses besides guidewires and catheters also punctureneedles which are thin, short hollow needles. The puncture needle (B)does not necessarily comprise a rod but can be embodied as a thin hollowtube made of epoxy resin and reinforced with glass fibers. Such apuncture needle can be regarded as a hollow rod wherein this punctureneedle can be doped in the same way as the above described rods. Therovings comprising a plurality of long glass fibers arranged in parallelcan be flattened before they are embedded in the epoxy resin for forminga puncture needle. Thereby a very small wall thickness can be achieved.

The puncture needles can also be produced by embedding thin rods into ahard matrix. Such a matrix can be e.g. epoxy resin. The thin rods andthe epoxy resin are co-micropultruded for production of the punctureneedles.

Independent of whether the puncture needle is embodied as a thin hollowtube made of epoxy resin and reinforced with glass fibers or whether itis produced by co-micropultrusion of flattened glass fibers in epoxyresin, the wall at the distal end of the puncture needle preferably isendowed with a thin, sharp edge. This edge can be provided by a hardlayer of polymer, e.g. a distinctly hard epoxy resin, covering the endof the puncture needle. Under this layer the glass fibers of thepuncture needle are securely covered and protected.

The rods, the matrix material and/or the glass fiber reinforced epoxyresin can be doped by any marker described in the examples of the rodsand medical devices as disclosed below. Also any combination of markersis possible. Likewise the puncture needles can be provided with theabove described coating containing gadolinium ions on their outersurface. Such a coating can also be provided on the inner surface of thehollow puncture needle.

The envelope polymer of the above described medical devices is made froma biocompatible material such as an elastic polymer material which isbased on polyurethane (PU) or a thermoplastic elastomer made from SEBS(styrene-ethylene-butylene-styrene-elastomer). Other appropriatepolymers are e.g. polyethylene, polypropylene, EVA, PVP and silicone. Asdescribed further below softer polymer materials can be advantageous incombination with MRI markers. If a softer polymer material is used asenvelope polymer then the rods have to be designed stiffer to compensatethe softer envelope polymer.

In the following the X-ray markers which were tested in prototypes areexplained:

-   -   Type 1: Doping of one rod 1/1 of the guidewire 5 or of one rod        of catheter 7 or another device with tungsten nanoparticles.    -   Type 2: Doping of envelope polymer with 5 to 80% barium        sulphate, preferably 20% to 40% barium sulphate, most preferably        40% barium sulphate.    -   Type 3: combination of types 1 and 2

The weight ratio of the doping particles and the matrix material 3,preferably epoxy resin, in case of tungsten nanoparticles preferably is1:1 to 2:1, and in case of iron microparticles preferably is 1:5 to1:100, more preferably 1:10 to 1:70, most preferably 1:30 to 1:60, ifnot specified differently, and in case of tungsten microparticlespreferably is 1:1 to 4:1, more preferably 2:1 to 3:1. In the followingthe weight ratio of the matrix material 3 and the doping particles iscalled “concentration”.

Tungsten microparticles can also be provided in the envelope polymer.With tungsten microparticels as an X-ray marker an envelope polymerbetter maintains its elasticity and becomes less brittle than beingdoped with barium sulphate. Therefore, tungsten microparticles are veryadvantageous if they are used to dope an envelope polymer, e.g. apolyurethane, with an X-ray marker.

X-ray markers can be included in all of the above listed medical devicesto obtain visibility in X-ray angiography and similar X-ray imagingprocedures comparable to current medical devices on the market whichcontain e.g. metal cores or metal braids. The concentration of the X-raymarkers is dependent on the design of the device, especially the volumeof the epoxy resin for Type 1 and of the envelope polymer 5 for Type 2,or the combination of these, respectively. For visualization in computertomography (CT) a lower amount of marker particles and/or less strongradiopaque marker particles are recommended. E.g., one rod doped with a2:1 concentration of tungsten nanoparticles alone has proven to besufficient for CT in guidewire prototypes. An image of a single roddoped with tungsten nanoparticles with a 2:1 concentration and having adiameter of 0.20 mm placed in a water phantom is shown in FIG. 4 a. Thisimage shows a clear and sharp image of the rod.

Examples of X-Ray Angiography Markers, e.g. For Guidewires andCatheters:1) tungsten nanoparticles with a concentration of 2:1 to 1:1 in one ormore rods and 40% barium sulfate in envelope polymer;2) tungsten nanoparticles with a concentration of 2:1 to 1:1 in one ormore rods and 20% barium sulfate in envelope polymer.

Other suitable X-ray markers are Barium (Ba), tantalum (Ta), osmium(Os), praseodymium (Pr), platinum (Pt), gold (Au), and lead (Pb).

FIG. 4 b shows images which were taken by X-ray angiography using awater phantom. The images are assigned with the numbers 1-4 wherein theimages show the following samples or devices:

Image 1: a single rod doped with tungsten nanoparticles with a 2:1concentration and a diameter of 0.20 mm.

Image 2: a guidewire with 40% barium sulphate in the envelope polymerand a central rod (33 Tex) doped with tungsten nanoparticles 2:1 with adiameter of 0.20 mm and three peripheral rods (33 Tex) doped with ironmicroparticles (<150 pm) with a 1:10 concentration and a diameter of0.17 mm; the diameter of the guidewire is 0.81 mm (0.032 inch).

Image 3: a Terumo reference guidewire with a nitinol core and a polymerenvelope (specification: REF-GA32263M); the diameter is 0.81 mm (0.032inch).

Image 4: a guidewire with 40% barium sulphate in the envelope polymer,an undoped central rod having a diameter of 0.20 mm and three peripheralrods (33 Tex) being doped with iron microparticles (<150 μm) in aconcentration of 1:10. The peripheral rods have a diameter of 0.17 mmand the guidewire has a diameter of 0.81 mm (0.032 inch).

The images 2 to 4 show the respective guidewire clearly and precisely.The image of the rod is rather vague. This shows that tungstennanoparticles are not sufficient for a one time X-ray exposure as it isperformed in X-ray angiography. Nevertheless, the contribution of thetungsten doped rod to signal intensity in X-ray angiography issignificant and useful.

In the following the MRI markers which were tested in prototypes areexplained:

The MRI markers used for doping of the rods and/or the envelope polymerare ferromagnetic, paramagnetic and diamagnetic particles. Ferromagneticand paramagnetic particles have positive magnetic susceptibilitycharacteristics. Such particles in the following are calledpassive-positive markers. Diamagnetic particles have negative magneticsusceptibility characteristics and are therefore called passive-negativemarkers. Passive-negative markers are for example barium sulphate andlead. Passive-positive markers are iron (Fe), iron oxide (FeO, Fe₂O₃,Fe₃O₄), cobalt (Co), nickel (Ni), molybdenum (Mo), zirconium (Zr),titanium (Ti), manganese (Mn), rubidium (Rb), aluminum (Al), palladium(Pd), platinum (Pt), chromium (Cr) or chromium dioxide (CrO₂). Thesemarkers due to their susceptibility characteristics have an influence onthe magnetic field in the direct vicinity of the rods or the medicaldevices. This local magnetic field influences the relaxation time ofprotons contained in adjacent water molecules. In the literature thereare also other classifications of MRI markers. E.g. it is referred toKanischka Ratnayaka et al., review “Interventional cardiovascularmagnetic resonance: still tantalizing”; Journal of CardiovascularMagnetic Resonance, Dec. 29, 2008, in which the MRI markers are definedby their effects on the image whether they cause negative contrastthrough local distortions of the magnetic field (black spots) orpositive contrast through enhanced local signal (bright spots). However,for describing the present invention it is preferred to define the MRImarkers according to the physical characteristics, namely susceptibilitycharacteristics.

Also iron-platinium alloy nanoparticles (FePt NPs) can be used aspassive-negative MRI markers. In Shu Chen et al.; “EngineeredBiocompatible Nanoparticles for in Vivo Imaging Applications” the use ofFePt NPs as contrast agent for MRI is described.

Passive MRI markers cause either negative contrast through localdistortions of the magnetic field (black spots) or positive contrastthrough enhanced local signal (bright spots). Ferromagnetic andparamagnetic particles, e.g. iron, iron oxide, nickel, aluminum andothers, are called passive negative markers which generate signal voidsfrom intentional magnetic susceptibility artifacts. Gadolinium,dysprosium and similar metals are passive positive markers as theyreduce the proton spin relaxation time of associated water molecules.Due to their specific characteristics and influences on the magneticproperties (especially the relaxation time) of the protons in the watermolecules located directly adjacent to the rods or medical devices theseMRI markers can be detected by common water-proton adjusted MRIsequences.

Prototypes of the rods and medical devices were tested in MRI systems.In these tests the rods and medical devices were placed in a water bath(water phantom) so that they were completely surrounded and covered bywater. This water phantom was placed into the magnetic field of an MRscanner. There are standard measuring conditions (“MR sequences”) in MRIsystems for detection of the position and properties of thewater-protons in the local magnetic field. With these standard sequencesthe rods and medical devices containing different MRI markers weretested. Standard MRI sequences employed on a Siemens Magnetom Symphony1.5 Tesla MR scanner essentially were:

1) T1 weighted sequence

SE 2D, TR/TE=420/14 ms, slice thickness: 2.0 mm, FOV=400×400 mm, matrix:512×256, phase FOV: 100%, percent sampling: 50%, bandwidth: 90 Hz/px,flip angle: 90°, TA=111 s, total number of slices: 15, spacing betweenslices: 2.2 mm (10%), phase encoding steps: 256

2) T2 weighted sequence

TSE (SE) 2D, TR/TE=3690/104 ms, slice thickness: 1.9 mm, FOV=400×400 mm,matrix: 512×307, phase FOV: 100%, percent sampling: 60%, bandwidth: 130Hz/px, flip angle: 180°, TA=90 s, total number of slices: 15, spacingbetween slices: 2.09 mm (10%), phase encoding steps: 345 (307), echotrain length (turbo factor): 15

3) VIBE Sequence

GRE/FLASH 3D, TR/TE=4.3/2.05 ms, slice thickness: 1.0 mm, FOV=400×300mm, matrix: 256×134, averages: 2, phase FOV: 75%, percent sampling:69.79%, bandwidth: 490 Hz/px, flip angle: 12°, TA=14 s, total number ofslices: 16, phase encoding steps: 134, slab thickness: 16

4) Gradient Echo Sequence (GRE)

GRE/FLASH 2D, TR/TE=700/12 ms, slice thickness: 2.5 mm, FOV=400×400 mm,matrix: 512×256, phase FOV: 100%, percent sampling: 50%, bandwidth: 65Hz/px, flip angle: 30°, TA=179 s, total number of slices: 15, spacingbetween slices: 2.75 mm (10%), phase encoding steps: 256

5) Real-time sequence

2D SSFP, >1 frame/s, TR/TE=2.2/4.7 ms, slice thickness: 5 mm,FOV=224×224 mm, matrix: 224×224, flip angle: 60°, voxel size 1×1 mm

FIG. 4 c shows four images A1, A2, B1 and B2 which were taken with a T2weighted sequence using a water phantom. The images A1 and A2 show asingle rod doped with iron oxide nanoparticles at a concentration of1:20 and the images B1 and B2 show a guidewire with a central rod (33Tex) doped with tungsten nanoparticles at a concentration of 2:1 andhaving a diameter of 0.20 mm and three peripheral rods (33 Tex) dopedwith iron oxide nanoparticles (<50 nm) at a concentration of 1:20 havinga diameter of 0.17 mm. The diameter of the guidewire is 0.81 mm (0.032inch). In the images A1 and B1 the rod or guidewire, respectively, isarranged orthogonally to the magnetic field B₀. The images A2 and B2were taken with the rod or guidewire, respectively, arranged in parallelto the magnetic field B₀. The artifact of the rod and guidewire in theimages A2 and B2 is very weak contrary to the images A1 and B1. Hence,when arranged orthogonally to the magnetic field B₀ of the MR scannerthey provided good results. However, if the nanoparticle containing rodsor guidewires are arranged in parallel to the magnetic field B₀ of theMR scanner they do not provide any reasonable signal except of adisplacement artifact. The nanoparticles are homogeneously distributedin the matrix material of the rods. Due to the high number of the smallnanoparticles the distance between neighbouring nanoparticles is verysmall. It is assumed that due to this small distance the magneticmoments are coupled to each other so that all the nanoparticles act asone bar magnet which extends in the longitudinal direction of the rodsor medical devices. If this is the case then the magnetic field in thedirect vicinity of the rods or the medical device containing the rods isonly very weakly influenced by the magnetism of the nanoparticlesbecause the magnetic field is concentrated inside the rods or medicaldevice. However, if the medical device is arranged orthogonally to themagnetic field B₀ of the MR scanner then the magnetic nanoparticles arealso coupled with each other and can be regarded as virtual bar magnets.However, then the bar magnets are arranged laterally to the longitudinaldirection of the rods. At the end of each virtual rod magnet themagnetic field is concentrated so that in the direct vicinity of therods or medical device the magnetic field is strongly influenced by themagnetism of the nanoparticles. Therefore, a rod doped withnanoparticles, particularly iron oxide nanoparticles, is only visible ifarranged orthogonally to the magnetic field B₀ of the MR scanner.Medical devices containing such rods can be used in open magnet MRscanners because in these the medical devices are used mainly in adirection orthogonal to the magnetic field B₀. Such rods or such amedical device produces a very sharp and precise image with nearly noartifacts in an open magnet MR scanner.

However, today most of the installed MR scanners are based on ringmagnets in which the medical devices should also be detectable if theyare arranged in parallel to the magnetic field B₀. Therefore, thedistance between the individual marker particles should be high enoughto avoid such a coupling and to also generate good signals in paralleldirection to the magnetic field B₀. To achieve such distances and tohave a sufficiently high doping effect the size of the marker particlesshould be larger.

Rods doped with iron particles with a diameter of 4-6 μm and with ironparticles sieved with a mesh of 150 μm, respectively, and guidewire testsamples containing such rods were tested. These guidewire test samplesconsisted of a polymer tube in which the rods are placed for simulatinga guidewire in an imaging process. The guidewire test samplesadditionally comprised one rod doped with tungsten nanoparticles(concentration 2:1, diameter 0.20 mm).

The images resulting from these tests are shown in FIG. 4 d and FIG. 4e. The images of FIG. 4 d show a rod doped with iron particles with adiameter of 4-6 μm (image A1, A2) and the rod doped with iron particlessieved with a mesh of 150 μm (image B1, B2). In the images A1 and B1 thetest samples were arranged orthogonally to the magnetic field B₀. In theimages A2 and B2 the test samples were arranged in parallel to themagnetic field B₀. The tests were carried out with a T2 weightedsequence in a water phantom. FIG. 4 e shows corresponding images of aguidewire test sample having one rod doped with iron microparticles (4-6μm, concentration 1:10 xdiameter 0.17 mm) in the images A1 and A2 and aguidewire test sample having a rod doped with iron microparticles sievedwith a mesh of 150 μm (concentration 1:10, diameter 0.17 mm) in theimages B1 and B2. These images were made applying a real-time sequenceand using an aortic phantom. In the images A1 and B1 the guidewire testsamples were arranged orthogonally to the magnetic field B₀ and in theimages A2 and B2 in parallel to the magnetic field B₀. As it can be seenin the images the test samples were visible independent of whether theywere arranged orthogonally or in parallel to the magnetic field B₀. Ironis a strong ferromagnet. Therefore, it makes the protons in watermolecules in the vicinity of the medical device visible in awater-proton adjusted MR sequence. Iron creates strong artifacts andthereby causes device images which are much broader than the deviceitself. This is the case particularly if the medical device or the rods,respectively, are arranged orthogonally to the magnetic field B₀ of theMRI imaging system.

With respect to the doping with passive MRI markers the goal is to havea) a strong signal and b) a confined and sharp signal. However, thestronger the signal is, the bigger are the artifacts which reduce thesharpness of the image. Preferably, the signal in parallel (strongenough) and orthogonal direction (not to broad) should be reasonablybalanced.

The following effects were found which influence the intensity and thesharpness of the signal:

-   -   The higher the concentration of the markers is, the stronger is        the signal.    -   The larger the particles are, the better is the balance between        imaging in parallel and orthogonal direction. However, the size        of the particles is limited by the production process of the        rods and/or the medical device. Particle sizes in the range of 1        μm to 150 μm are most appropriate. Preferably, the particles        have a size of at least 1 μm, 2 μm, 5 μm, 10 μm or 50 μm. Good        results are also achieved with particles which are sieved with a        mesh of 150 μm. Furthermore a mesh of about 80-130 μm is also        suitable.    -   A plurality of doped rods provides a stronger signal than only a        single rod comprising the same or even a higher amount of marker        particles. FIG. 4 f shows a guidewire test sample comprising one        rod doped with tungsten nanoparticles in a concentration of 2:1        and a diameter of 0.20 mm and three rods (image B1, B2) doped        with iron particles sieved with a mesh of 150 μm in a        concentration of 1:10 and a diameter of 0.17 mm and another        guidewire test sample comprising the same kind of rods but with        only one rod doped with tungsten and one rod doped with iron        particles (image A1, A2). FIG. 4 g shows images of a guidewire        test sample having one rod doped with tungsten nanoparticles        (concentration 2:1, diameter 0.20 mm) and one rod doped with        iron microparticles sieved with a mesh of 150 μm (concentration        1:10, diameter 0.17 mm) in the images A1 and A2 and a guidewire        test sample having one rod doped with tungsten nanoparticles        (concentration 2:1, diameter 0.20 mm) and three rods doped with        iron microparticles sieved with a mesh of 150 μm (concentration        1:100, diameter 0.17 mm) in the images B1 and B2. These images        were made applying a real-time sequence and using an aortic        phantom. Although the higher doped rod according to the images        A1 and A2 of FIG. 4 g contains ten times the amount of marker        particles than the lower doped rods according to the images B1        and B2 of FIG. 4 g, the three lower doped rods together cause a        stronger signal than the one higher doped rod. This can be        explained in that the plurality of doped rods is localized        further apart in the medical device so that the range of        influence onto the magnetic field covers a broader area.        Therefore, more voxels (which are detected by the MR scanner)        are influenced by the plurality of rods. Concluding, an        increased number of voxels is blackened in comparison to a        guidewire having only one doped rod. More blackened voxels mean        a visually broader and stronger signal.

The distance of the marker particles or rods, respectively, from thesurrounding water molecules influences the sharpness and intensity ofthe signal. The larger the distance between marker particles andneighbouring water molecules is, the weaker is the influence of themagnetic field on these water molecules. In other words, the thicker thelayer of an envelope polymer is with which the rods are covered in themedical device, the sharper the signal will be. Thus the position of therods in the medical device has a strong influence on the sharpness ofthe signal.

FIG. 6 shows images A and B which were taken with a T2 weighted sequenceusing a water phantom. FIG. 7 shows similar images A and B which weretaken with a Gradient echo sequence (GRE). The images A and B in bothfigures show the following samples numbered with 1-7:

-   1. rod shaped body, 33 Tex, OD 0.17 mm (=Outer Diameter) (without    envelope polymer);-   2. rod shaped body, 66 Tex, OD 0.24 mm (without envelope polymer);-   3. stiff guidewire, OD 0.88 mm;-   4. standard guidewire, OD 0.81 mm;-   5. micro guidewire, OD 0.31 mm;-   6. standard guidewire, OD 0.81 mm; inserted into a tube with ID 1.5    mm (=Inner Diameter) and OD 2.3 mm;-   7. standard guidewire, OD 0.81 mm; inserted into a tube with ID 0.94    mm and OD 1.45 mm;

All guidewire samples contain rods doped with iron particles 40-63 μm ata concentration of 1:50. The standard guidewire comprises a central rodwith 33 Tex glass fiber. The stiff guidewire comprises a central rodwith 66 Tex glass fiber. The micro guidewire comprises a rod with 66 Texglass fiber covered by a thin envelope polymer (PU). It must be notedthat the amount of the matrix material is approximately proportional tothe amount of glass fibers.

Therefore, rods having 66 Tex glass fiber comprise more matrix materialthan rods having 33 Tex glass fiber. As the concentration of the markerin the matrix material is always the same the rods having 66 Tex glassfiber absolutely contain more marker particles than rods having 33 Texglass fiber.

The samples 6 and 7 comprise a guidewire being inserted into a tube. Thetubes are sealed so that no water can penetrate into the air gap betweenguidewire and tube wall. Sample 6 encloses a relevant air gap. In sample7 the air gap between the tube and the guidewire is small.

In image A the samples are arranged longitudinally to the magnetic fieldB₀ and in image B orthogonally to the magnetic field B₀.

The rods (samples 1 and 2) show a broad artifact. Also the microguidewire (sample 5) having only a thin envelope polymer shows a broadartifact. The artifacts generated by the standard and stiff guidewiresare significantly smaller.

The larger air gap of sample 6 causes a black artifact which adds to theartifact of the MRI marker so that the image of the sample is darker incomparison to the sample 7 with a small air gap.

By comparing the samples 4 and 7 it can be seen that the tube coveringthe guidewire with only a small air gap reduces the width of theartifact. These results demonstrate that the envelope polymer of theguidewires (sample 3 and 4) and the tube (sample 7) reduce the width ofthe artifacts compared to the respective rods. This is caused by thelarger distance between the water molecules surrounding the respectivesample and the passive-negative MRI marker particles. The larger thedistance is the smaller is the artifact.

As the rod shaped bodies in a medical device mostly are arranged indifferent positions with respect to the center of the medical device itis preferred that the rod shaped bodies positioned more distant to thecenter of the medical device contain no passive-negative MRI marker.This principle is embodied in a guidewire preferably in such a way thatthe rod shaped body containing a passive-negative MRI marker is locatedin the center of the guidewire. If the guidewire comprises several rodshaped bodies then it is useful if the rod shaped bodies being not inthe center do not comprise passive-negative MRI markers.

This principle can also be applied to a catheter. If a cathetercomprises at least one rod shaped body having a passive-negative MRImarker then this rod shaped body is positioned at the inner section ofthe catheter. Rod shaped bodies having no passive-negative MRI markermay be positioned closer to the circumferential surface of the catheter.Such a catheter or tube can also be embodied of at least two concentriclayers wherein only the most inner layer comprises a passive-negativeMRI marker.

The width of the artifact is mainly determined by the distance of thepassive-negative MRI marker to the circumferential surface of themedical device as the magnetic influence of the marker on thesurrounding water molecules detected in MRI depends on this distance.This is also valid for catheters and tubes as the water moleculessurrounding the outer surface of the medical device determine the outerborder of the artifacts and not the water molecules in the inner lumenof a catheter or tube. The distance between the section containing apassive-negative MRI marker and the outer circumferential surface of themedical device preferably is at least 0.1 mm, more preferably at least0.2 mm and most preferably at least 0.3 mm.

These effects can be exploited in different combinations to achieve theabove mentioned aim of a strong and sharp signal. Basically, the size ofthe particles should be sufficiently large to balance the signalsdetected in longitudinal and orthogonal direction to the magnetic fieldB₀ of the MR scanner.

A strong and comparably confined and sharp signal can be achieved whenthe absolute amount of marker particles is kept rather low anddistributed in several peripheral rods.

Another possibility is to embody the medical device with a central rodor with the rods positioned closest to the center of the medical devicebeing doped with a passive MRI marker and having peripheral undoped rods(which contain no passive MRI marker) or rods doped with an X-raymarker. FIG. 4 h comprises an image A and B, wherein in each image threeindividual rods 1, 2, 3 are shown, each being doped with ironmicroparticles (<150 μm, concentration 1:10, diameter 0.17 mm). The rod2 is uncovered. The rod 1 is covered by a thick layer of epoxy resin, sothat the total diameter of this sample is 0.9 mm. The rod 3 is coveredby a thick layer of polyurethane polymer. The total diameter of thissample is also about 0.9 mm. Image A shows the rods arrangedorthogonally to the magnetic field B₀ and image B in parallel to themagnetic field B₀. In the image A it is clearly visible that theuncovered rod causes a much broader signal than the two other coveredrods. As the rods 1 and 3 are covered by an envelope polymer themagnetic field distortion outside of the medical device is attenuated.As a result only a comparably small layer of surrounding water moleculesis influenced by the iron particles in the rod, compared to a reasonablythicker layer when the marker particles are located in the peripheralrods close to the outer boundary of the medical device. The thicker thelayer of influenced water molecules is, the broader is the resultingsignal/artifact. Concluding, the MR image of the medical device has amultiple of its actual diameter. In case of a medical device in whichthe central rod comprises the MRI marker particles a sufficiently strongand sharp image is obtained, having only a minimally larger diameterthan the actual diameter of the device.

These designs of the medical device are based on the influence of themagnetic field caused by the passive-negative marker particles on theprotons in the water molecules present in the direct vicinity of themedical device.

Another approach to obtain a strong, confined and sharp signal isadjustment of the MR sequence. If the relaxation echoes of protons inthe envelope polymer and not of those in the surrounding water moleculesare detected a very sharp image limited almost to the actual diameter ofthe medical device can be obtained. This is most preferable e.g. for thetips of puncture or biopsy needles where absolutely precise operation ofthe device to target small e.g. cancer tissue regions is required. Hardpolymer materials such as epoxy resins or the above mentionedpolyurethane (PU) or thermoplastic elastomer made from SEBS contain aplurality of protons but relaxation times for these protons are much toshort in hard polymers due to the stiffness of the materials in order tobe detected with currently established MR sequences and scanners.Instead of these relatively hard polymer materials softer polymermaterials can be used as envelope polymer for the medical devicesaccording to the invention. In softer polymers the protons are a bitmore flexible and have somewhat longer relaxation times. Consequently,they can be detected with current MR scanners and MR sequence software.E.g. PVC or rubber materials are appropriate for that purpose. Rubbermaterials due to the cross-linked polymer chains provide a sufficientlyhigh stability but the protons of rubber materials still have asufficiently long relaxation time. The use of such rubber materials inan MR scanner is described in R. Umathum et al., Rubber Materials forActive Device Tracking, Abstract 16^(th) ISMRM Congress 2008 in Toronto(The International Society for Magnetic Resonance in Medicine). Suchrubber materials can also be extruded, wherein the vulcanization of therubber material is carried out after the extrusion.

There are also known rubber-like solid hydrogels, such as PVA-H, whichprovide a very good visibility. However, the strength of such hydrogelsis low. Another design of the guidewire comprises a core of such arubber-like solid hydrogel which is enclosed by the envelope polymer. Inthe envelope polymer one or more rods can be integrated. In such aguidewire the mechanical stability is mainly defined by the tube-likeenvelope polymer. In an MR scanner the core of the guidewire provides asignal. This signal can be influenced by doping the core of theguidewire or by means of doped rods in the envelope polymer.

One advantage of using a soft polymer or a rubber polymer as envelopepolymer of a medical device or of using a core made of a soft polymer,rubber or a rubber-like solid hydrogel is that the relaxation time issufficiently long to be detected in an MR scanner. As the relaxationtime differs significantly from the relaxation time of water thesematerials can be detected by a shorter echo time than that for waterresulting in two images which can be overlaid. Thereby, the medicaldevice can be distinctly presented, e.g. in a specifically selectedcolour, and different from the body tissue and blood which is presentedas used to in black, white and shades of grey. Additionally, the usercan individually select one of the two images to be separately displayedon the screen. Therefore, it is possible to control the position of themedical device in the body by superimposing both images but it is alsopossible to have an image of the body tissue alone which is notdisturbed by the medical device.

A further advantage for visualization of medical devices in MRI guidedinterventions can be realized if e.g. a guidewire comprises a softerpolymer as described above as the envelope polymer but a correspondinglyused catheter comprises a harder polymer as the wall-forming polymer. Inthat case the guidewire is detected with a short echo time resulting ina sharp signal almost precisely delineating its boundaries. The catheteris detected with a longer echo time detecting the artifact resultingfrom the surrounding water molecules. The two devices may be presentedin different colours which very easily enables distinguishing of thecatheter from the guidewire.

The following MRI marker particles were used for doping of the rods andthe envelope polymer:

-   -   Tungsten nanoparticles: American Elements; Tungsten Nanopowder,        99%, <100 μm (typically 40-60 nm), spherical; product code:        W-M-01-NP    -   Tungsten microparticles: Sigma-Aldrich; Tungsten, powder, 99.9%,        12 μm; product code: 267511    -   Iron microparticles: Riedel de Haen (Sigma-Aldrich), <150 μm;        product code: 12312    -   Iron microparticles: Roth, 4-6 μm; product code: 3718.0    -   Iron oxide nanoparticles: Sigma-Aldrich, <50 nm; product code:        544884    -   Barium Sulphate (e.g. in commercially available “Tecoflex with        BaSO4” or “Mediprene with BaSO4”)

The following materials were used for production of rods and medicaldevices:

-   -   High temperature resistant epoxy resin    -   Tecoflex™ is an elastic polymer material which is based on        polyurethane (PU).    -   Mediprene® is a thermoplastic elastomer made from SEBS        (styrene-ethylene-butylene-styrene-elastomer) which is primarily        used for medical purposes. Mediprene is offered by Elasto AB,        Sweden.    -   Glass fibers    -   Aramide fibers

The medical devices were produced by co-extrusion wherein the envelopepolymer is extruded together with the rods. As the rods shall not bedeformed during the co-extrusion the rods were made from a hightemperature resistant material. However, if the envelope polymer isbased on a rubber material then the extrusion temperature can be reducedso that the temperature requirements for the matrix material arecorrespondingly reduced and other resin materials than high temperatureresistant epoxy resin are suitable. These other resin materials can beregular epoxy resin, PVC or synthetic rubber.

LIST OF REFERENCE NUMERALS

-   -   1 Rod shaped body    -   1/1 Central rod    -   1/2 Peripheral rod    -   2 Filament    -   3 Matrix polymer    -   4 Cord    -   5 Guidewire    -   6 Envelope polymer    -   7 Catheter

1.-15. (canceled)
 16. Rod shaped body comprising one or morenon-metallic filaments and a non-ferromagnetic matrix material, whereinthe matrix material encloses and/or agglutinates the filaments, whereinat least one of said non-metallic filaments is a ht-fiber.
 17. Rodshaped body according to claim 16, wherein the matrix material enclosesand/or agglutinates marker particles for generating a signal in an X-rayor magnetic resonance imaging process.
 18. Rod shaped body according toclaim 16, wherein the non-metallic filaments comprises at least oneglass fiber.
 19. Rod shaped body, according to claim 16, comprising oneor more non-metallic filaments and a non-ferromagnetic matrix material,wherein the matrix material encloses and/or agglutinates the filaments,and marker particles for generating a signal in an X-ray or magneticresonance imaging process, wherein the one or more non-metallicfilaments extend along the major part of the rod shaped body.
 20. Rodshaped body according to claim 16, characterized in that thenon-metallic filaments are arranged in parallel to each other.
 21. Rodshaped body according to claim 16, characterized in that thenon-metallic filaments comprise glass-fibers or/and polyamide or/andaramide fibers.
 22. Medical device comprising one or more rod shapedbodies according to claim 16, and an envelope polymer in which the rodshaped bodies are embedded.
 23. Medical device according to claim 22,comprising one or more rod shaped bodies, each comprising one or morenon-metallic filaments and a non-ferromagnetic matrix material, and anenvelope polymer in which the one or more rod shaped bodies areembedded, wherein a cord is embedded either in the matrix material or inthe envelope polymer, wherein the cord is more flexible than thenon-metallic filaments.
 24. Medical device, according to claim 22,comprising several rod shaped bodies, each comprising one or morenon-metallic filaments and a non-ferromagnetic matrix material, whereinthe matrix material encloses and/or agglutinates the filaments andmarker particles for generating a signal in an X-ray or magneticresonance imaging process, and an envelope polymer in which the rodshaped bodies are embedded, wherein the rod shaped bodies are arrangedin different positions with respect to the center of the medical deviceand the rod shaped bodies which are arranged closer to the center of themedical device comprise non-metallic filaments having a higher tensilemodulus than the non-metallic filaments of the rod shaped bodies whichare positioned more distant to the center of the medical device. 25.Medical device, according to claim 22, wherein the medical devicecomprises an elongated body made of a polymer material and the polymermaterial encloses a passive-negative MRI marker consisting of markerparticles for generating an artifact in a magnetic resonance imagingprocess wherein the passive-negative MRI marker is located only in acentral section of the medical device, wherein the distance of thepassive-negative MRI marker to the outer surface of the medical deviceis at least 0.1 mm.
 26. Medical device according to claim 25, comprisingrod shaped bodies, each comprising one or more of said non-metallicfilaments and a non-ferromagnetic matrix material, wherein said matrixmaterial encloses and/or agglutinates the filaments and marker particlesfor generating a signal in an X-ray or magnetic resonance imagingprocess, and an envelope polymer in which the rod shaped bodies areembedded, wherein the rod shaped bodies are arranged in differentpositions with respect to the center of the medical device and the rodshaped bodies positioned more distant to the center of the medicaldevice contain no passive-negative MRI marker.
 27. Medical deviceaccording to claim 25, wherein the medical device is either a guidewirehaving a rod shaped body comprising a passive-negative MRI marker andbeing positioned at the center of the guidewire, or a catheter or tubehaving either at least one rod shaped body comprising a passive-negativeMRI marker and being positioned at the inner section of the catheter oris embodied of at least two concentric layers, wherein only theinnermost layer comprises a passive-negative MRI marker.
 28. Medicaldevice according to claim 27, wherein the medical device is embodied assaid catheter having at least two concentric layers, one of said layersis reinforced by non-metallic filaments being twisted, braided, or wovento a spatial structure, wherein the non-metallic filaments compriseht-fibers.
 29. Medical device according to claim 25, wherein the MRImarker is selected from the group of ferromagnetic and paramagneticparticles with particle sizes in the range of 1 μm to 150 μm. 30.Medical device according to claim 22, comprising several rod shapedbodies for reinforcing the medical device, and an envelope polymer inwhich the rod shaped bodies are embedded, wherein the medical devicecomprises marker particles for generating an artifact in a magneticresonance imaging process, and the envelope polymer is a soft polymer orrubber material or PVC.
 31. Medical device according to claim 22,particularly a guidewire, comprising a flexible tip.
 32. Medical deviceaccording to claim 31, comprising a metallic core or metallic particlesin the flexible tip.
 33. A medical device according to claim 22, whereinMRI markers are provided at the tip of the device to cause MRI artifactswith a higher intensity than the MRI markers in the residual part of themedical device.
 34. Rod shaped body according to claim 16, wherein thenon-metallic filaments comprise several glass fibers and severalht-fibers.
 35. Rod shaped body, according to claim 16, comprising one ormore non-metallic filaments and a non-ferromagnetic matrix material,wherein the matrix material encloses and/or agglutinates the filaments,and marker particles for generating a signal in an X-ray or magneticresonance imaging process, wherein the one or more non-metallicfilaments extend along the major part of the rod shaped body, and thelength of the non-metallic filaments is at least half of the length ofthe rods.
 36. Medical device according to claim 25, wherein the MRImarker is selected from iron microparticles with particle sizes in therange of 1 μm to 150 μm.